Evidence map›Paper›PMID 40827126›Full record

ReviewAlzheimer's & dementia (New York, N. Y.)

Sex differences and the role of estrogens in the immunological underpinnings of Alzheimer's disease.

Brittani R Price, Keenan A Walker, Jaclyn M Eissman, Vidyani Suryadevara, Lindsey N Sime, Timothy J Hohman, Marcia N Gordon

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Alzheimer's & dementia (New York, N. Y.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Brittani R PriceMedical Affairs, Pharmaceutical Diagnostics GE HealthCare Marlborough Massachusetts USA.
Keenan A WalkerLaboratory of Behavioral Neuroscience National Institute on Aging Baltimore Maryland USA.
Jaclyn M EissmanVanderbilt Memory & Alzheimer's Center Vanderbilt University Medical Center Nashville Tennessee USA.
Vidyani SuryadevaraDepartment of Radiology Molecular Imaging Program at Stanford Stanford University Stanford California USA.
Lindsey N SimeDepartment of Translational Neuroscience College of Human Medicine Michigan State University Grand Rapids Michigan USA.
Timothy J HohmanVanderbilt Memory & Alzheimer's Center Vanderbilt University Medical Center Nashville Tennessee USA.
Marcia N GordonDepartment of Translational Neuroscience College of Human Medicine Michigan State University Grand Rapids Michigan USA.ORCID https://orcid.org/0000-0002-4051-9283

Funding

Geroscience approaches to mitigate tauopathy in aged mouse brainR01AG062217 · NIA · MICHIGAN STATE UNIVERSITY · PI GORDON, MARCIA N · 2018 to 2022
$3.0M
NIA NIH HHS R01 AG062217
6 · The paper itself

Abstract

Alzheimer's disease (AD) affects women more frequently and more severely than men, but the biological mechanisms underlying these sex differences remain poorly understood. This review integrates recent findings from neuroscience, immunology, endocrinology, and genetics to explore how sex steroid hormones, particularly estrogen, shape neuroimmune responses and influence AD risk. We highlight the pivotal roles of microglia and astrocytes, whose inflammatory and neuroprotective actions are modulated by hormonal fluctuations across the female lifespan, including pregnancy, menopause, and menopausal hormone replacement therapy. Key genetic risk factors, such as apolipoprotein E ε4, show sex-specific effects on glial activation, tau pathology, and cognitive decline. Furthermore, life-stage transitions, especially menopause, intersect with changes in brain metabolism, immune signaling, and epigenetic regulation, increasing susceptibility to neurodegeneration in women. We propose a framework for sex-aware, personalized approaches to AD prevention and treatment. By integrating hormone-immune interactions with genetic and glial biology, this review emphasizes the critical need for sex-specific models in AD research. Highlights: Women develop greater tauopathy, with more cognitive and clinical consequences in Alzheimer's disease (AD).Glial activation is adapted by estrogens to shape vulnerability or resilience to AD.Sex differences in innate and adaptive immunity could contribute to AD progression.Effects of menopausal hormone therapy on immunity in AD remain understudied.Future studies to explore sex differences in immune function during AD are needed.

Indexed as

adaptive immunityapolipoprotein Eastrocytescognitive declineestradiolestrogeninnate immunitymenopausemicroglianeuroinflammation

Identifiers

PMID40827126
PMCPMC12358009

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.